Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings

• Published in: Surgery 1995-08, Vol.118 (2), p.406-411
• Main Authors: Barber, Annabel E., Coyle, Susette M., Fischer, Eva, Smith, Christopher, Poll, Tom van der, Shires, G. Tom, Lowry, Stephen F.
• Format: Article
• Language: English
• Subjects: Adult; Blood - metabolism; Endotoxins - pharmacology; Humans; Hydrocortisone - blood; Lipopolysaccharides - pharmacology; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - metabolism; Solubility; Time Factors; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/S0039-6060(05)80352-6

Background. We have previously reported that the antecedent administration of glucocorticoids altered both the hormonal and proinflammatory cytokine responses to lipopolysaccharide (LPS) when administered to human volunteers. In that study, subjects with vastly exaggerated levels of tumor necrosis factor (TNF) and interleukin (IL)-6 12 and 144 hours after cortisol infusion exhibited hemodynamic and hormonal responses no different from those of untreated subjects after endotoxin. The current study examined levels of the antiinflammatory cytokines interleukin-1 receptor antagonist (IL-1ra) and soluble receptors to tumor necrosis factor (sTNF-R) in the same setting of the previous report. Methods. Hydrocortisone succinate was infused into healthy volunteers. LPS was then injected immediately or was delayed by 6, 12, or 144 hours (C, C-6, C-12, and C-144, respectively). Subjects receiving LPS alone served as controls. Plasma was analyzed to determine levels of TNF, sTNF-R and IL-1ra by enzyme-linked immunosorbent assay before administration of LPS and at 30-minute intervals after administration of LPS for 6 hours. Results. Levels of sTNF-R increased after LPS administration in all groups (p